Serum amyloid P deposition is a sensitive and specific feature of membranous-like glomerulopathy with masked IgG kappa deposits.
Serum amyloid P deposition is a sensitive and specific feature of membranous-like glomerulopathy with masked IgG kappa deposits.
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DOI：
10.1016/j.kint.2019.10.026
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发表时间：
2020-03
影响因子：
19.6
通讯作者：
Arthur JM
中科院分区：
文献类型：
--
作者：
Larsen CP;Sharma SG;Caza TN;Kenan DJ;Storey AJ;Edmondson RD;Herzog C;Arthur JM
膜样肾小球病伴掩盖性IgG kappa沉积（MGMID）是最近描述的一种具有独特组织病理学的肾小球肾炎模式。该模式的特征在于上皮下和/或系膜免疫沉积物被“掩蔽”，通过常规免疫荧光对免疫球蛋白染色，但在蛋白酶消化后对IgG和κ轻链强烈染色。这种类型的肾小球肾炎患者最常见于年轻女性，表现为蛋白尿和自身免疫性疾病（如低滴度抗核抗体）的模糊病史。在这里，我们比较了9例MGMID肾活检的激光捕获显微切割肾小球与8例显示膜性肾小球病其他模式的活检的质谱图谱。MGMID中最显著增加的蛋白质是血清淀粉样蛋白P。免疫组化显示血清淀粉样蛋白P与MGMID肾小球中的IgG共定位，但不与PLA 2 R相关的膜性肾小球病共定位。血清淀粉样蛋白P在所有32例MGMID活检的肾小球中均为阳性，但在其他类型的膜性肾小球病（如与PLA 2 R和THSD 7A相关的肾小球病）活检中为阴性。在173例活检中，有4例活检显示肾小球血清淀粉样蛋白P染色不符合MGMID或淀粉样变性的标准。所有4例血清淀粉样蛋白P染色阳性的活检标本均为膜性肾小球病伴IgG κ沉积，与MGMID的区别仅在于缺乏“掩蔽”。因此，肾小球沉积物中血清淀粉样蛋白P的阳性染色鉴定了一种独特形式的肾小球肾炎，可能具有共同的疾病病理生理机制。
Membranous-like glomerulopathy with masked IgG kappa deposits (MGMID) is a recently described pattern of glomerulonephritis with a unique histopathology. The pattern is characterized by subepithelial and/or mesangial immune deposits that are “masked”, to immunoglobulin staining by routine immunofluorescence but strongly stain for IgG and kappa light chain after protease digestion. Patients with this pattern of glomerulonephritis are most commonly young females presenting with proteinuria and a vague history of autoimmune disease such as low titer antinuclear antibodies. Here we compared the mass spectrometry profile of laser capture microdissected glomeruli from nine MGMID renal biopsies with eight biopsies showing other patterns of membranous glomerulopathy. The protein most significantly increased in MGMID was serum amyloid P. Immunostaining showed serum amyloid P colocalized with IgG in the glomeruli of MGMID but not with PLA2R-associated membranous glomerulopathy. Serum amyloid P was positive in the glomeruli of all 32 MGMID biopsies but negative in biopsies of other types of membranous glomerulopathies such as those associated with PLA2R and THSD7A. There were four biopsies with glomerular serum amyloid P staining among the 173 biopsies that did not fulfill criteria for MGMID or amyloidosis. All four of these biopsies with positive serum amyloid P staining had a membranous pattern of glomerulopathy with IgG kappa deposits that only differed from MGMID by the lack of “masking”. Thus, positive staining within glomerular deposits for serum amyloid P identifies a unique form of glomerulonephritis likely sharing a common pathophysiologic mechanism of disease.